The new Bioassay Core (Core C) will provide bioassay support for all Projects with an array of validated, robust, and efficient bioassays, which have been previously established in Project 2. The following specific aims are proposed: 1. Evaluate botanical extracts for their chemopreventive properties. We will analyze the antioxidative activity, the NAD(P)H:quinone oxidoreductase 1 (NQ01) inducing properties, the antiinflammatory activity, and aromatase enzyme inhibiting properties of the extracts/compounds. When extracts/compounds will be active in the NQ01 assay, we will analyze these samples in the antioxidative response element luciferase assay and in the glutathione-S-transferase induction assay. The induction of several Phase I metabolism enzymes is regulated by the xenobiotic response element (XRE). Inducer of Phase I enzymes interfere with the metabolism of other drugs and endogenous estrogen;therefore, the extracts will be tested in the XRE-luciferase assay. 2. Evaluate botanical extracts/compounds for hormonal activity (efficacy). The alkaline phosphatase assay in Ishikawa cells will be employed as the major assay to test the botanicals for estrogenic and antiestrogenic activities. Active fractions will be analyzed for estrogen receptor (ER)a and ERB selectivity in an ERa and ERB-ERE-luciferase assay in breast cancer cells. If promising samples have been found, we will test for ER ligands in the ERa and ERB competitive radioactive binding assay. As progestogenic activity is important for endometrium protection, the progesterone response element luciferase and progesterone receptor competitive binding assay will be conducted. Finally, the selective serotonin reuptake inhibition assay (SSRI) will be employed, since SSRIs have been described to alleviate menopausal symptoms. 3. Evaluate botanicals for their distribution profile, safety, and efficacy in vivo. When active extracts/compounds have been determined, the ovariectomized rat model to analyze the distribution and metabolism profile (Project 3), the safety, and efficacy will be performed. With these assays. Core C directly supports the whole Center efforts by establishing toxic, interfering, and active compounds, thus providing bioactive marker compounds for the standardization of new botanicals.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Specialized Center (P50)
Project #
2P50AT000155-11
Application #
8007079
Study Section
Special Emphasis Panel (ZAT1-SM (19))
Project Start
1999-09-30
Project End
2015-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
11
Fiscal Year
2010
Total Cost
$180,947
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Li, Guannan; Simmler, Charlotte; Chen, Luying et al. (2017) Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci 109:182-190
Nikoli?, Dejan (2017) CASMI 2016: A manual approach for dereplication of natural products using tandem mass spectrometry. Phytochem Lett 21:292-296
Nikoli?, Dejan; Macias, Carmen; Lankin, David C et al. (2017) Collision-induced dissociation of phenethylamides: role of ion-neutral complexes. Rapid Commun Mass Spectrom 31:1385-1395
Liu, Yang; Friesen, J Brent; Grzelak, Edyta M et al. (2017) Sweet spot matching: A thin-layer chromatography-based countercurrent solvent system selection strategy. J Chromatogr A 1504:46-54

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